Role of Tyrosine Kinase in Fibroblast Compaction and Cerebral Vasospasm

2000 ◽  
pp. 227-230
Author(s):  
A. Patlolla ◽  
K. Ogihara ◽  
A. Zubkov ◽  
K. Aoki ◽  
A. D. Parent ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Cerebral Vasospasm

A REVIEW ON THE ROLE OF TYROSINE KINASE INHIBITORS AVAILABLE FOR THE MANAGEMENT OF CHRONIC MYELOID LEUKEMIA

2020 ◽  
Vol 7 (2) ◽  
pp. 205-211
Author(s):  
Kaynat Fatima ◽  
Syed Tasleem Raza ◽  
Ale Eba ◽  
Sanchita Srivastava ◽  
Farzana Mahdi
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Protein Kinases ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

The function of protein kinases is to transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Many of these kinases are linked to the initiation and development of human cancer. The recent development of small molecule kinase inhibitors for the treatment of different types of cancer in clinical therapy has proven successful. Significantly, after the G-protein-coupled receptors, protein kinases are the second most active category of drug targets. Imatinib mesylate was the first tyrosine kinase inhibitor (TKI), approved for chronic myeloid leukemia (CML) treatment. Imatinib induces appropriate responses in ~60% of patients; with ~20% discontinuing therapy due to sensitivity, and ~20% developing drug resistance. The introduction of newer TKIs such as, nilotinib, dasatinib, bosutinib, and ponatinib has provided patients with multiple options. Such agents are more active, have specific profiles of side effects and are more likely to reach the necessary milestones. First-line treatment decisions must be focused on CML risk, patient preferences and comorbidities. Given the excellent result, half of the patients eventually fail to seek first-line treatment (due to discomfort or resistance), with many of them needing a third or even further therapy lines. In the present review, we will address the role of tyrosine kinase inhibitors in therapy for chronic myeloid leukemia.

Classic and Novel Signaling Pathways Involved in Cancer: Targeting the NF-κB and Syk Signaling Pathways

2019 ◽  
Vol 14 (3) ◽  
pp. 219-225 ◽  
Author(s):  
Cong Tang ◽  
Guodong Zhu
Keyword(s):  
Cancer Therapy ◽  
Tyrosine Kinase ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Cell Receptor ◽  
Transmembrane Receptors ◽  
Biological Responses ◽  
Different Types

The nuclear factor kappa B (NF-κB) consists of a family of transcription factors involved in the regulation of a wide variety of biological responses. Growing evidence support that NF-κB plays a major role in oncogenesis as well as its well-known function in the regulation of immune responses and inflammation. Therefore, we made a review of the diverse molecular mechanisms by which the NF-κB pathway is constitutively activated in different types of human cancers and the potential role of various oncogenic genes regulated by this transcription factor in cancer development and progression. We also discussed various pharmacological approaches employed to target the deregulated NF-κB signaling pathway and their possible therapeutic potential in cancer therapy. Moreover, Syk (Spleen tyrosine kinase), non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immune-receptors like the B-cell receptor (BCR), which can also activate the inflammasome and NF-κB-mediated transcription of chemokines and cytokines in the presence of pathogens would be discussed as well. The highlight of this review article is to summarize the classic and novel signaling pathways involved in NF-κB and Syk signaling and then raise some possibilities for cancer therapy.

Role of tyrosine kinase in insulin release in an insulin secreting cell line (INS-1)

1995 ◽  
Vol 7 (5) ◽  
pp. 505-512 ◽  
Author(s):  
E.J. Verspohl ◽  
B. Tollkühn ◽  
H. Kloss
Keyword(s):  
Tyrosine Kinase ◽  
Cell Line ◽  
Insulin Release ◽  
Secreting Cell

scholarly journals TRIM31 facilitates K27-linked polyubiquitination of SYK to regulate antifungal immunity

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xueer Wang ◽  
Honghai Zhang ◽  
Zhugui Shao ◽  
Wanxin Zhuang ◽  
Chao Sui ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Fungal Pathogen ◽  
Essential Role ◽  
Molecular Mechanisms ◽  
Systemic Infection ◽  
Lectin Receptors ◽  
Innate And Adaptive Immunity ◽  
Cytokines And Chemokines

AbstractSpleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase, which plays an essential role in both innate and adaptive immunity. However, the key molecular mechanisms that regulate SYK activity are poorly understood. Here we identified the E3 ligase TRIM31 as a crucial regulator of SYK activation. We found that TRIM31 interacted with SYK and catalyzed K27-linked polyubiquitination at Lys375 and Lys517 of SYK. This K27-linked polyubiquitination of SYK promoted its plasma membrane translocation and binding with the C-type lectin receptors (CLRs), and also prevented the interaction with the phosphatase SHP-1. Therefore, deficiency of Trim31 in bone marrow-derived dendritic cells (BMDCs) and macrophages (BMDMs) dampened SYK-mediated signaling and inhibited the secretion of proinflammatory cytokines and chemokines against the fungal pathogen Candida albicans infection. Trim31−/− mice were also more sensitive to C. albicans systemic infection than Trim31+/+ mice and exhibited reduced Th1 and Th17 responses. Overall, our study uncovered the pivotal role of TRIM31-mediated K27-linked polyubiquitination on SYK activation and highlighted the significance of TRIM31 in anti-C. albicans immunity.

scholarly journals Proline-rich tyrosine kinase 2 mediates transforming growth factor-beta-induced hepatic stellate cell activation and liver fibrosis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jonghwa Kim ◽  
Wonseok Kang ◽  
So Hee Kang ◽  
Su Hyun Park ◽  
Ji Young Kim ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Tyrosine Kinase ◽  
Focal Adhesion ◽  
Transforming Growth Factor ◽  
Family Members ◽  
Type I ◽  
Tyrosine Kinase 2 ◽  
The Impact ◽  
Tgf Β1

AbstractHepatic fibrogenesis is characterized by activation of hepatic stellate cells (HSCs) and accumulation of extracellular matrix (ECM). The impact of ECM on TGF-β-mediated fibrogenic signaling pathway in HSCs has remained obscure. We studied the role of non-receptor tyrosine kinase focal adhesion kinase (FAK) family members in TGF-β-signaling in HSCs. We used a CCl4-induced liver fibrosis mice model to evaluate the effect of FAK family kinase inhibitors on liver fibrosis. RT-PCR and Western blot were used to measure the expression of its target genes; α-SMA, collagen, Nox4, TGF-β1, Smad7, and CTGF. Pharmacological inhibitors, siRNA-mediated knock-down, and plasmid-based overexpression were adopted to modulate the function and the expression level of proteins. Association of PYK2 activation with liver fibrosis was confirmed in liver samples from CCl4-treated mice and patients with significant fibrosis or cirrhosis. TGF-β treatment up-regulated expression of α-SMA, type I collagen, NOX4, CTGF, TGF-β1, and Smad7 in LX-2 cells. Inhibition of FAK family members suppressed TGF-β-mediated fibrogenic signaling. SiRNA experiments demonstrated that TGF-β1 and Smad7 were upregulated via Smad-dependent pathway through FAK activation. In addition, CTGF induction was Smad-independent and PYK2-dependent. Furthermore, RhoA activation was essential for TGF-β-mediated CTGF induction, evidenced by using ROCK inhibitor and dominant negative RhoA expression. We identified that TGF-β1-induced activation of PYK2-Src-RhoA triad leads to YAP/TAZ activation for CTGF induction in liver fibrosis. These findings provide new insights into the role of focal adhesion molecules in liver fibrogenesis, and targeting PYK2 may be an attractive target for developing novel therapeutic strategies for the treatment of liver fibrosis.

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